The progression of solid cancer to invasive tumor is the major prerequisite in metastasis, and involves changes in cell morphology and motility and the like. Although genetic modification in cancer cells is varied according to the type of metastatic cancer, it causes common result of cancer cells being separated from its originating organ and dispersed in various organs. Under such tumor microenvironment, various growth factors, angiogenesis factors, and proteases are secreted by cancer cells and cancer associated cells, and they induce cancer growth and angiogenesis and decompose extracellular matrix to promote cancer cell invasion and metastasis. In addition, osteopontin (OPN), tenascin C, and matricellular proteins contribute to tumor metastasis, and regulate the maintenance and expansion of normal or tumor stem cells and metastatic niches. As an alternative to targeting a specific stage of cancer progression, it can be considered to select a molecule performing an important function in a plurality of stages of cancer development and target it. Among these molecules, periostin is considered as an important protein regulating cell adhesion and interaction of cells and matrix.
Periostin is one of extracellular matrix proteins, and it is secretory protein that is involved in cell adhesion, acts as cytokine and transduces signals through cell adhesion molecules integrin αvβ3 and αvβ5. At first, it is discovered as osteoblast specific factor, and is highly expressed in periosteum of bone tissue. Since periostin is overexpressed in various epithelial carcinoma such as breast cancer, and the function is related to the critical stages of malignant process such as metastasis and angiogenesis, recently, there is a rising interest in periostin. Although periostin is not expressed in normal breast cell line, the expression is specially increased in the case of breast cancer. And, periostin is an important limiting factor during metastatic colonization, promotion of cell survival, angiogenesis and the maintenance of tumor stem cells. Many clinical studies show that the overexpression of periosin and increase in serum concentration of periostin are related to metastatic tumor growth and bad prognosis. In addition, periostin is an important limiting factor that promotes cell survival, angiogenesis and the maintenance of tumor stem cells during metastatic colonization. Thus, periostin was confirmed as a promising candidate substance related to the inhibition of tumor growth and metastasis.
Biologically targeted therapy has been a main stream of cancer treatment for last 20 years. Compared to the existing therapy exhibiting toxicity even to normal cells, targeted therapy receives attention as more effective therapy because it is more specific and has low toxicity to normal cells. Nucleic acid-based aptamers are on the rise as targeted therapeutic molecules. Aptamer is a single strand DNA or RNA, and very closely and specifically binds to a target molecule. Aptamer is developed by a repeated selection method named SELEX (Systematic evolution of ligands by exponential enrichment), and it selectively recognizes its target and binds thereto using a specific three-dimensional structure. Aptamer can regulate the function of a protein target by directly binding to the target. Due to the nature of short nucleic acid, aptamer has advantages in terms of improved stability, convenience in production and modification, low immunogenicity and low toxicity and the like, compared to other therapeutic means. Thus, the value of aptamer is being recognized as an alternative to low molecule and antibody-based therapy.
Accordingly, there is a demand for development of periostin on the rise as a promising anticancer target, aptamer specifically binding thereto, and anticancer therapeutic technology using the same.